rs10493565

Positions:

• chr1-75234086-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001130058.2(SLC44A5):​c.753T>C​(p.Ile251=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,610,428 control chromosomes in the GnomAD database, including 61,116 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6347 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54769 hom.)
• Consequence: SLC44A5 NM_001130058.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

Genes affected

SLC44A5 (HGNC:28524): (solute carrier family 44 member 5) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.704 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A5	NM_001130058.2	c.753T>C	p.Ile251=	synonymous_variant	12/24	ENST00000370859.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A5	ENST00000370859.8	c.753T>C	p.Ile251=	synonymous_variant	12/24	2	NM_001130058.2	A1
SLC44A5	ENST00000370855.5	c.753T>C	p.Ile251=	synonymous_variant	12/24	1		P4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42770 AN: 151842 Hom.: 6335 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.284

GnomAD3 exomes AF: 0.250 AC: 62615 AN: 250364 Hom.: 8558 AF XY: 0.254 AC XY: 34422 AN XY: 135360

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.0674

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.269 AC: 392624 AN: 1458468 Hom.: 54769 Cov.: 31 AF XY: 0.270 AC XY: 195761 AN XY: 725736

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.0668

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.282 AC: 42831 AN: 151960 Hom.: 6347 Cov.: 32 AF XY: 0.279 AC XY: 20723 AN XY: 74282

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.0663

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.281

Alfa AF: 0.274 Hom.: 13643

Bravo AF: 0.279

Asia WGS AF: 0.181 AC: 631 AN: 3478

EpiCase AF: 0.274

EpiControl AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.039
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10493565; hg19: chr1-75699771; COSMIC: COSV63760233;